Endocrine Pancreas Pathology

Question 1

Pancreas Histology
Cell Types (6) with Secretions

Answer 1

Alpha Cells: Secrete Glucagon
Beta Cells: Secrete Insulin
Delta Cells: Secrete Somatostatin
PP Cells: Secrete Pancreatic Polypeptide

D1 Cells: Secrete Vasoactive Intestinal Polypeptide (VIP)
Enterochromaffin Cells: Secrete Serotonin

Question 2

Glucose Homeostasis

Insulin Release Pathway (4) and Incretins (2)

Answer 2

GLUT2 Receptors bring glucose into Beta cells
Glucose metabolized, ATP made
ATP inhibits K+ channels causing depolarization
Ca2+ influx causes insulin release

Incretins stimulated by oral glucose
Stimulate insulin release via Glucose dependent insulin-releasing polypeptide

Question 3

Insulin Actions

Muscle (3) Liver (3) Adipose (3)

Answer 3

Muscle:
Increased Glucose Uptake
Increased Glycogen and Protein Synthesis

Liver:
Decreased Gylcogenolysis
Increased Glycogen synthesis
Increased Lipogenesis

Adipose:
Increased Glucose uptake
Increased Lipogenesis
Decreased Lipolysis

Question 4

Diabetes Mellitus

Definition and Diagnostic Criteria (4)

Answer 4

Impairment of normal glucose homeostasis from insulin resistance or insufficiency causing hyperglycemia

A1C > 6.5%
Fasting glucose > 126
Oral glucose tolerance test > 200 at 2 hours
Random glucose > 200

Question 5

Type 1 Diabetes
Pathogenesis, Genetics, Demographics (2) Histology (3)
Clinical Features (7)

Answer 5

T cell dysregulation creates autoantibodies to Beta cells

Genetic linkage to MHC Class II

Normal or underweight Children and adolescents

Inflammatory T cell and Macrophage infiltrate
Beta cell depletion
Islet atrophy

Symptoms present after 90% destruction:
Polydipsia
Polyuria
Polyphagia
Fatigue
Weight loss
Diabetic ketoacidosis

Question 6

Type 2 Diabetes

Pathogenesis (4), Genetics (3) Demographics (2) Pancreas Histology (2) Clinical Features (6)

Answer 6

Peripheral insulin resistance leading to beta cell failure
Adipokines, Free Fatty Acids, Inflammation all contribute

Diabetogenic genes: TCF7L2, PPARG, FTO

Centrally/Viscerally Obese people, mostly adults

Pancreatic scarring
Amyloid deposition

Polydipsia
Polyuria
Polyphagia
Fatigue 
Vision changes
Nonketotic hyperosmolar coma

Question 7

Maturity Onset Diabetes of the Young

Demographic, Clinical Features (3) and Mutation

Answer 7

Children and adolescents

Hyperinsulinemia
No islet antibodies
Nonketotic hyperosmolar coma

Glucokinase loss of function mutation

Question 8

Type A Insulin Resistance

Mutation, Clinical Features (4)

Answer 8

Insulin receptor mutations

Hyperinsulinemia
Acanthosis nigricans
Polycystic ovaries
Elevated androgen levels

Question 9

Gestational Diabetes
Related Risks (5)

Answer 9

C section
Macrosomia
Neonatal hypoglycemia causing seizures and coma
Congenital malformations
Stillbirth

Question 10

Diabetic Ketoacidosis

Pathogenesis (5), Clinical Features (6) and Treatment (3)

Answer 10

Insulin deficiency causes increased lipolysis
Increased FFA’s causes ketone formation
Epinephrine release blocks insulin action and causes glucagon secretion
Hyperglycemia causes osmotic diuresis causing dehydration and shock which releases more Epi

Hyperglycemia
Ketonuria
Metabolic acidosis 
Nausea/Vomiting
Tachycardia 
Kussmaul respirations

Insulin
Hydration
Potassium

Question 11

Hyperglycemic Hyperosmotic Syndrome

Pathogenesis (3) and Presentation (6)

Answer 11

Prolonged insulin deficiency causes hyperglycemia via increased gluconeogenesis and decreased glucose uptake
Hyperglycemia leads to osmotic diuresis

Hyperglycemia > 600
Severe dehydration
Impaired renal function
Hyperosmolarity 
Altered mental status
Coma

Question 12

Diabetic Hypoglycemia

Etiologies (3) and Symptoms (5)

Answer 12

Missed meals
Overexertion
Too much insulin

Dizziness
Confusion
Sweating 
Palpitations
Tachycardia

Question 13

Chronic Complications of Diabetes (5)

Answer 13

Stroke
Myocardial Infarction (main cause of death)
Lower Extremity gangrene
Retinopathy: via neovascularization
Nephropathy

Question 14

Advanced Glycation End Products
Pathologic Effects (5)

Answer 14

Increase:
TGF-beta and VEGF
Reactive oxygen species
Coagulation factors
Smooth muscle proliferation
Atherogenesis via cross linking matrix proteins

Question 15

Diabetic Nephropathy

Lesions (3), Complication with Description (3) Diagnosis

Answer 15

Glomerular Sclerosis
Renal Vascular Lesions
Pyelonephritis

Kimmelsteil-Wilson Disease:
Thickened glomerular basement membrane
Reduced ability to filter
Albuminuria

Urine Albumin:Creatinine ratio

Question 16

Pancreatic Neuroendocrine Tumors
Common Morphology (3) and Prognosis

Answer 16

Grossly tan
Small round blue cell tumors
Have secretory granules

All are MALIGNANT

Question 17

Insulinoma

Prevalence, Clinical Features (6) Morphology (3) Diagnosis (2)

Answer 17

Most common pancreatic neuroendocrine tumor

Hypoglycemia:
Dizziness
Confusion
Sweating 
Palpitations
Tachycardia

Solitary tumor
Amyloid deposition
Focal/Diffuse Islet hyperplasia

Elevated levels of insulin and C peptide

Question 18

Gastrinoma - Zollinger Ellison Syndrome
Clinical Features (4) and Behavior

Answer 18

Islet cell tumor
Gastric acid hypersecretion
Peptic ulcers unresponsive to PPI treatment
Diarrhea

Often locally invasive or metastatic at time of diagnosis

Question 19

Somatostatinoma
Clinical Features (3)

Answer 19

Diabetes (reduced insulin)
Cholelithiasis (reduced GB motility)
Steatorrhea (reduced lipase)

Question 20

Glucagonoma
Clinical Features (4)

Answer 20

Diabetes
Depression
DVTs
**Dermatitis: Necrolytic migratory erythema of groin and LE

Question 21

VIPoma
Clinical Features (4) and Tumor Association

Answer 21

Watery Diarrhea
Hypokalemia
Aclorhydria
Flushing

Neural crest tumors

Question 22

Pancreatic Carcinoid Tumor
Clinical Features (2)

Answer 22

Elevated serotonin

Atypical carcinoid syndrome

Question 23

Pancreatic Polypeptide-Secreting Tumors
Clinical Features (2)

Answer 23

Asymptomatic

Present as mass lesions